Randomized Phase 2 Study Of Epcoritamab Vs Watch And Wait InPatients With Previously Untreated Low Tumor Burden FollicularLymphoma

ELIGIBILITY CRITERIA * Histologically diagnosed follicular lymphoma grade 1-3a * Within 6 months from the diagnosis of follicular lymphoma * Have no prior systemic treatment for lymphoma * Stage II (non-contiguous), III or IV disease * Age ≥18 years * Performance status ≤2 on the ECOG scale * Low-tumor burden disease based on GELF criteria26 \> No nodal or extranodal (except spleen) mass \> 7 cm in its greater diameter * No 3 nodal or extranodal sites ≥ 3 cm in diameter * No presence of at least one B symptom ▪ B symptoms: Fever (\>38 ℃), night sweats, weight loss \> 10% in the past 6 months * No symptomatic splenomegaly (or size \>16 cm) * No impending organ compression or involvement (ureteral, orbital, gastrointestinal) * None of the following cytopenias due to bone marrow involvement of lymphoma ▪ Hemoglobin ≤ 10 g/dL ▪ Platelets ≤ 100 x 109/L ▪ Absolute neutrophil count (ANC) \< 1.5x109/L * No pleural effusion or ascites * Normal LDH * Bi-dimensionally measurable disease, with at least one nodal lesion ≥ 1.5 cm or one extranidal lesion \> 1 cm in longest diameter by CT, PET/CT, and/or MRI * Participants must have adequate organ and marrow function as defined below: \> Total bilirubin ≤ 2.0 x upper limit of normal (ULN), unless consistent with Gilbert's (ratio between total and direct bilirubin \> 5) * AST and ALT ≤ 3 x ULN * Alkaline phosphatase ≤ 3 x ULN * Creatinine ≤ 2 x ULN for reasons other than lymphoma * Blood counts below if without bone marrow lymphoma involvement * Hemoglobin ≥ 8 g/dL * Platelets ≥ 75 x 109/L * Absolute neutrophil count (ANC) ≥ 1.5x109/L * All subjects must \> Agree to refrain from donating blood while on study treatment, during dose interruptions and for at least 12 months following the last dose of study treatment. * Ability to understand and the willingness to sign an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarker. * Females must agree to abstain from breastfeeding during study participation and for at least 12 months after epcoritamab discontinuation. * Females of childbearing potential (FCBP) must: * Have one negative pregnancy tests via serum or urine prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, prior to day 1 of each cycle, and after end of study therapy. This applies even if the subject practices true abstinence\* from heterosexual contact. * Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice. Otherwise, she must agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting epcoritamab, during the study treatment (including dose interruptions), and for at least 12 months after the last dose of epcoritamab. * Male subjects must: * A male subject who is sexually active with a female with reproductive potential must agree to use a barrier method of birth control, eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ suppository (including dose interruptions), even if they have undergone a successful vasectomy, from the time of signing consent, for the duration of the study, and for at least 12 months after the last dose of epcoritamab. A male subject must agree not to donate sperm or semen, while taking epcoritamab, during breaks (dose interruptions), and for at least 12 months after the last dose of epcoritamab. EXCLUSION CRITERIA * Known active central nervous system lymphoma or leptomeningeal disease * Any prior history of other malignancy besides B-NHL, unless the participant has been free of disease for ≥ 3 years and felt to be at low risk for recurrence by the treating physician, except: * Adequately treated localized skin cancer without evidence of disease. * Adequately treated breast cancer without evidence of disease. * Adequately treated prostate cancer or monitored with watch and wait for low risk disease without evidence of progressive disease. * Adequately treated cervical carcinoma in situ without evidence of disease. * Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk * Uncontrolled human immunodeficiency virus (HIV), or active Hepatitis C Virus, or active Hepatitis B Virus infection, or any uncontrolled active significant infection, including suspected or confirmed JC virus infection and SARS-CoV2 * Participants with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded. Subjects with a history of Hepatitis C who received antiviral treatment are eligible as long as PCR is negative. * History of immunodeficiency (with the exception of hypogammaglobulinemia) or concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of \>10mg/day of prednisone) within 28 days of the first dose of study drug * Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study * Significant screening electrocardiogram (ECG) abnormalities including, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block. * History of stroke, seizure disorder or participants requiring antiepileptic therapy or intracranial hemorrhage within 6 months prior to study entry. * Participants with more than mild pericardial effusion confirmed by ECHO. * Lactating or pregnant women * Administration of any investigational agent within 28 days of first dose of study drug. * Participants who have undergone major surgery within 28 days or minor surgery within 3 days of first dose of study drug. * Participants taking chronic corticosteroids for other diseases, unless administered at a dose equivalent to \< 10 mg/day prednisone. For corticosteroids, prednisolone \>20 mg daily (or equivalent) qualifies as immunosuppressive and thus is excluded for this use. Note: corticosteroids at any dose are permitted for control of lymphoma-related symptoms, including during screening, and for prophylaxis or AE management during the trial. * Life expectancy \< 6 months * Prior exposure to epcoritamab or other CD3X CD20 bispecific, independently from indication * Participants who have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. * Participants who have a history of (non-infectious) pneumonitis that require steroids or has current pneumonitis. * Participants with psychiatric illness/social situations that would limit compliance with study requirements.